Arthritis Pain Drug Should Be Pulled Due to Adverse Heart Effects: Study

TORONTO -- Researchers are calling for the removal of a widely
used pain medication from worldwide markets due to a high risk of
heart attack and other adverse cardiovascular events associated
with the drug.

Diclofenac, a non-steroidal anti-inflammatory drug, or NSAID, is
often prescribed for relieving the pain and inflammation of
arthritis.

But the researchers say diclofenac, which is sold under a
variety of brand names, including Voltaren in Canada, carries an
almost identical risk of serious cardiovascular side-effects as
Vioxx.

Vioxx was a highly touted and highly promoted NSAID that ended
up being pulled from the market by its maker, Merck, after a
patient trial showed it was linked to an increased rate of heart
attacks and strokes.

"This is a drug that should be taken off the market, it needs to
go," Dr. David Henry, CEO of the Institute for Clinical Evaluative
Sciences (ICES) in Toronto, said Tuesday of diclofenac.

"This drug increases the risk of heart attack by about the same
degree as Vioxx did. And Vioxx was withdrawn from world markets in
2004 by the manufacturer because of that risk," said Henry, who has
a background in clinical pharmacology and has studied NSAIDs for
about two decades.

"So this drug is still there, very widely used, and
internationally the most popular drug despite having an almost
identical cardiovascular risk profile to a drug that was taken off
the market eight years ago."

In a paper published in this week’s edition of PLoS
Medicine, Henry and co-author Dr. Patricia McGettigan of the London
School of Medicine and Dentistry outline the cardiovascular risks
of various anti-inflammatory painkillers, based on an analysis of
numerous studies.

They found that people taking diclofenac have a 40 per cent
higher risk of having a heart attack than those taking naproxen,
considered the safest NSAID choice for minimizing cardiovascular
risk.

For people with underlying heart disease, taking diclofenac
significantly raises the risk of heart attack, said Henry.

While diclofenac makes up a respectable proportion of NSAIDs
sold in Canada, the U.K. and Australia, the researchers’
biggest concern is about low- and middle-income countries in Asia
and South Asia, where the drug commands a huge market share.

"What ... we wanted to know was how extensively it was used in
those countries that now are experiencing a major epidemic of
cardiovascular disease," said Henry, pointing to such countries as
China and India.

"We’re talking about vast populations where this drug and
others are available very cheaply and are widely used. And we
wanted to know whether these high-risk drugs -- diclofenac’s
not the only one, there’s an equivalent drug called
etoricoxib -- are still being used.

"Between them, they have a third of the entire market," he said,
noting that etoricoxib is not sold in North America.

In China, for instance, diclofenac is the most commonly used
NSAID in hospitals and its popularity has huge public health
implications, the authors say.

"If it were taken by only one per cent of China’s
population of approximately 1.3 billion annually, based on the
relative risk calculations ... it could cause 14,000 additional
unintended deaths," they write.

"These deaths are preventable -- lower-risk NSAIDs, including
naproxen and low-dose ibuprofen, are widely available and are
equally efficacious. Both are available as generic products."

The researchers have been raising a red flag about diclofenac in
medical journal studies for several years, but regulatory agencies
in countries around the world have been slow to label the drug as
being high-risk.

In fact, many countries continue to keep it on their essential
medicines lists, which encourages doctors to continue prescribing
the drug despite evidence of its risks to heart health.

In New Zealand and Bangladesh, for instance, diclofenac makes up
43 per cent of all NSAIDs sold. In Canada, the drug has a 17 per
cent market share.

Henry said the researchers have petitioned the World Health
Organization to list naproxen as the preferred NSAID, based on its
safer cardiovascular side-effect profile.

"And hopefully that will affect the pick-up in the essential
medicines lists which are developed in each of the countries," he
said.